Currently, little is known about the restorative processes that occur in the brain during stroke rehabilitation. The goal of the proposed studies is to generate an improved understanding of these processes in order to refine treatments that promote stroke recovery. The proposed research will take advantage of the excellent spatial and temporal resolution of functional MRI (fMRI) to precisely measure the location and magnitude of brain restorative processes. Observed changes in brain functional organization will be correlated with neurological and functional assessments of recovery. The specific aims of the proposed research are as follows: Specific aim number 1: to test the hypothesis that fMRI of subjects with good recovery from stroke will demonstrate patterns of brain organization different from those seen in normals. Our pilot data suggest that several brain areas are recruited in subjects with good stroke recovery. The specificity of data from subjects with good recovery will be assessed by comparing these results with those obtained from subjects with poor recovery. An MRI-compatible device invented by our group will be used to measure motor performance during fMRI scanning. Specific aim number 2: to test the hypothesis that serial changes in fMRI scans correlate with serial changes in clinical status. A good correlation at the time of clinical improvement would imply that the fMRI activations are a reliable marker for effective recovery mechanisms. Continued brain reorganization after plateau of clinical course could have therapeutic implications for stroke rehabilitation. Specific aim number 3: to test the hypothesis that fMRI activations seen after a stroke occur exclusively in regions with normal cerebral blood flow and normal cerebrovascular reserve. The fMRI method to be used is dependent on a coupling between neuronal activity and vascular reactivity. Cerebrovascular disease is highly prevalent in our subjects, however, and could alter this coupling. Therefore cerebral blood flow and vasoreactivity will be evaluated to aid interpretation of the fMRI studies. The proposed studies seek to identify where restorative processes take place in the brain and at what time points during clinical recovery these processes are changing. The long term goal is to apply the findings from the proposed research to design clinical trials aimed at maximizing long term stroke outcomes. The proposed research will be performed at three sites: (1) Massachusetts General Hospital (Boston, MA) has an active stroke service, valuable for initially identifying patients and for the continued study of cerebrovascular disease. (2) Spaulding Rehabilitation Hospital (Boston, MA) has large physiatry and stroke rehabilitation services, creating an ideal setting for serially examining stroke subjects and their treatments. (3) MGH-NMR Center (Charlestown, MA), located two miles from (1) and (2), is a pioneering fMRI center.